I. EXECUTIVE SUMMARY The Core, under the leadership of Dr. Bruce Aronow, has provided innovative bioinformatics service, training, and collaboration with Center investigators who focus on understanding the genetic basis of digestive system functions and diseases. With the evolution from a Digestive Disease Research Development Core Center to a Silvio O. Conte DDRCC - locally known as the Cincinnati Digestive Health Center (DHC) - the Core has supported a strong focus on translational research in pediatric digestive disease. Core faculty are members of the Division of Biomedical Informatics - the home of state-of-the-art computational infrastructure and a hub of bioinformatics research and training for the Cincinnati Children's Research Foundation (CCRF). The Core provides support for data processing, analysis, and results interpretation for research studies that use technologies that include gene expression microarrays, NexGen sequencing, RT-PCR, microarray-based SNP genome-wide association analysis, protein quantification based on technologies including Luminex and MALDI-TOF mass-spectrometry, and also protein structure prediction for the characterization of significant domains and residues, protein-protein and protein-drug interactions. To do this, the Bioinformatics Core uses an array of resources that are physically managed by infrastructure specialists within the Division of Biomedical Informatics. DHC investigators have direct access to Core services, and they receive support that is personalized and directed to the needs of their projects so as to optimize gains in knowledge from not only their own genetic and genomics data but also as leveraged by multiple other internal and external studies data. Investigative outcomes have also been improved by making Core consultative services available at concept stages; during selection of genetics and genomics platforms; by stringent quality control assessment; and by comprehensive data mining, results interpretation; discussion of appropriate validation, experimental extrapolation, and publication. The Core serves research needs of projects in all four focus areas of the DHC: 1) Chronic Liver Diseases, 2) Inflammatory and Diarrheal Diseases, 3) Obesity and the digestive system, and 4) Development and digestive diseases. To cite a few examples, Bioinformatics Core-enabled studies have generated new insight into the molecular basis and mechanisms of biliary atresia-associated tissue injury and disease phenotypes, inflammatory bowel disease, eosinophilic esophagitis (EE), and nonalcoholic fatty liver disease - all of which are diseases of complex pathogenesis and causes of substantial morbidity and mortality in children - and has also provided important contributions into studies probing the basic developmental biology and translational implications of gastrointestinal stem and progenitor cell formation and function in vivo and in vitro. To empower DHC investigators, the Core also regularly sponsors bioinformatics training via hands-on workshops that are well-subscribed and lead to vigorous engagement and collaboration. The Core leadership has been innovative in their goal to enhance DHC investigators' studies. Meeting the needs of DHC projects has been a driving force behind separately-funded projects that developed novel computational tools to analyze and infer critical genes and mechanisms responsible for diseases, such as GATACA, Toppgene, and Toppcluster, an integrative suite of tools for aggregating, mining and visualizing knowledge of genes, pathways, and disease phenotypes. Application of these tools has provided exciting enhancements to projects by DHC investigators that use genomic technologies. Combining DHC investigators data with extensive other available data such as from the NCBI GEO has led to the development of the Digestome Database whose aim is to enable DHC investigators to perform data analysis and mining to form new hypotheses and understanding of digestive system development and diseases. Working with the Gene and Protein Expression Core, and with a substantial commitment from CCRF, the Core has now implemented rich integrated tools for the analysis of next generation sequencing-derived data including exome sequencing, RNA-seq, and ChIP-seq, and these are already in use by DHC investigators in EE, IBD, and stem cell-related projects. Thus, this summary underscores a dynamic Bioinformatics Core that provides state-of-the-art service to DHC investigators, acts as a nidus of collaboration and innovation, and continues to evolve to support investigators' use of advanced genetic and genomic technologies to facilitate new discoveries in digestive disease critical for human health.